Share Facebook
Crohn's Disease Forum » Books, Multimedia, Research & News » Granulomas obstruct lymphatics in all layers of the intestine in Crohn's disease.


11-10-2014, 03:54 AM   #1
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
Granulomas obstruct lymphatics in all layers of the intestine in Crohn's disease.

http://www.ncbi.nlm.nih.gov/pubmed/24730532

Granulomas obstruct lymphatics in all layers of the intestine in Crohn's disease.

2014 Nov

Van Kruiningen, Hayes AW, Colombel JF

Department of Pathobiology and Veterinary Science, University of Connecticut

After an earlier study defining immunolabeled lymphoid follicles, obstructed lymphatics, and granulomas of the diseased ilea of 24 Crohn's disease patients, we chose to trace the lymphatics of these cases and 10 additional by serial sectioning. Particular attention was given to establishing physical continuity between granuloma-obstructed lymphatics and lymphatics with 'lymphocytic thrombi'. Formalin-fixed paraffin-embedded tissue blocks from resected diseased ilea and proximal colons from 34 patients were reviewed. Patients were 13 men and 21 women, aged 14-60 years. Duration of disease ranged from 1 month to 10 years. Immunohistochemistry employed D2-40 antibody to label lymphatics and anti-CD68 to label granulomas. Twenty-nine of the 34 (85%) resection tissues had lymphangectasia, in mucosa, submucosa, and subserosa. In 53% of the specimens, lymphatics of the various layers were obstructed by granulomas that filled the lumina. In 44%, 15/34, there were also distended lymphatics that were totally plugged with lymphocytes. In 10 of the 15, serial sections revealed continuity between the lymphocyte-plugged lymphatics and the endolymphatic granulomatous obstruction downstream. In 5 of the cases, D2-40 immunostaining revealed redundant lymphatic endothelium interwoven with the granuloma cells. Granulomas totally obstruct lymphatics in all layers of the intestine in Crohn's disease. Upstream of these obstructions, lymphatics are distended with lymphocytes. The degree and extent of this potentially irreversible 'lymphangitis nodosa' have undoubtedly confounded treatment regimens and clinical trials. There currently are no imaging methods to demonstrate the lymphangitis, nor treatments to resolve it.
11-10-2014, 09:15 AM   #2
Pilgrim
Senior Member
 
Pilgrim's Avatar
 
Join Date: Jul 2014
Location: Ontario

My Support Groups:
Well, I thanked you for the post, but in my heart don't want to see it. When our kid had her biopsies at 3 yrs old, there were multiple granulomas identified already at that point. I wonder what this study might imply for her outcomes and treatment.
__________________
Mom to daughter,age 5, diagnosed at age 3 with Crohn's Disease
Current Treatment: Humira (started 12/2014) moved to weekly injections (07/2015), Back to 50% EN orally. Zinc supplements. Calprotectin through the roof.
Previous Treatment: Azathioprine (discontiued 09/14 due to Pancreatitis) Flagyl, Sulfasalazine, EEN, Iron,Vit D, Zinc, SCD
11-10-2014, 11:23 AM   #3
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
Same here by the age of 7 in multiple locations
__________________
DS - -Crohn's -Stelara -mtx-IVIG
11-10-2014, 01:08 PM   #4
Pilgrim
Senior Member
 
Pilgrim's Avatar
 
Join Date: Jul 2014
Location: Ontario

My Support Groups:
Hers were in multiple locations in the large intestine - well as far as they went in. But upper scope was clear. Was it the same for your son?

Any change in scope results after Humira?
11-10-2014, 01:15 PM   #5
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
The granuloma seen during diagnosis are "normal" in the sense that you'd expect them to be there with crohn's disease. Their pattern isn't very different from the groupings you see in tuberculosis.

It's the lymphatics V. Kruiningen is interested in, the first signs of crohn's disease are related to the lymphatics. You see these small inflamed follicles in an otherwise uninflamed mucosa in people who have been diagnosed very early. I have posted pictures of them before, they're like a an inflamed flower pattern that isn't seen in any other intestinal disease. You don't see it in most people, because by the time someone is diagnosed, they already have inflamed mucosa and patches of inflamed tissue with granuloma, it's hard to see what is causing what at that point, however, sometimes on routine checks or with people who are diagnosed really early, you can see the inflamed follicles.

That same lymph system and the peyer's patches are most active during the teenage years. The dilation of the lymphatics surrounding the intestine, the obstruction of lymphatics with immune cells, the ability of bacteria to abuse dilated lymph vessels, and the subsequent inflammation might be all related to each other. Lymphangiectasia.

Last edited by kiny; 11-10-2014 at 01:37 PM.
11-10-2014, 01:35 PM   #6
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
this is early crohn's disease, usually when ppl are diagnosed the mucosa is inflamed by then

here all you see is a little inflamed dot, it's a lymph follicle, this is where immune cells are concentrated, where many lymphocites are concentrated, this is where the adpative immune system can be trigered

this is one of my favorite pictures, it shows that early onset crohn's disease starts with inflamed lymph follicles and the peyer's patches

11-10-2014, 01:43 PM   #7
Pilgrim
Senior Member
 
Pilgrim's Avatar
 
Join Date: Jul 2014
Location: Ontario

My Support Groups:
I just went in to look at my daughters scope pictures - some are similar to this, you can see the inflamed dots but they are in clusters to make a larger region. Very interesting.
11-10-2014, 01:46 PM   #8
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
Another reason why ppl are so interested in those follicles and peyer's patches is because they

A: are most active during teenage years, which is the best explanation so far why everyone seems to get crohn's disease around those years

B: they're almost exclusively found in the ileum, which explains why crohn's disease is very often in the ileum or profimal colon

C: they're an entry point for bacteria

D: the dilaton of the lymph vessels, is seen in animals, they get symptoms like diarreha, inflamed intestine, etc
11-10-2014, 01:47 PM   #9
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
I just went in to look at my daughters scope pictures - some are similar to this, you can see the inflamed dots but they are in clusters to make a larger region. Very interesting.
was it a picture of the ileum?
11-10-2014, 01:49 PM   #10
Crohn2357
Senior Member
 
Crohn2357's Avatar
 
Join Date: Aug 2013

My Support Groups:
this is early crohn's disease, usually when ppl are diagnosed the mucosa is inflamed by then

here all you see is a little inflamed dot, it's a lymph follicle, this is where immune cells are concentrated, where many lymphocites are concentrated, this is where the adpative immune system can be trigered

this is one of my favorite pictures, it shows that early onset crohn's disease starts with inflamed lymph follicles and the peyer's patches

What is the importance of this? Would you explain?
11-10-2014, 01:51 PM   #11
Pilgrim
Senior Member
 
Pilgrim's Avatar
 
Join Date: Jul 2014
Location: Ontario

My Support Groups:
No, it wasn't. The photos are her large intestine only to the splenic flexure.
11-10-2014, 01:53 PM   #12
kiny
Senior Member
 
kiny's Avatar
 
Join Date: Apr 2011
What is the importance of this? Would you explain?
I'd just be repeating what I said in the thread though. It explains why crohn's disease is isolated in most people around the ileum and proximal colon, because that's where those follicles are concentrated. It shows the entry point bacteria probably use. It shows otherwise healthy mucosa, there's no widespread self-antigen response of tissue. It's more evidence that supports a form of lymphangiectasia in crohn's disease.
11-10-2014, 03:24 PM   #13
Malgrave
Senior Member
 
Malgrave's Avatar
 
Join Date: Jul 2012
Location: Belgium

My Support Groups:
Interesting that our children were so young with granulomas MLP and Pilgrim. My son was 3 also when first granulomas were found. After this finding the doctors wanted to exclude chronic granulomatous disease (because he was so young) and two years later, in another hospital, they wanted to exclude mycobacterial infection (standard procedure with little IBD patients in that hospital). CGD was excluded but atypical mycobacterial infection was found!
__________________
*Son (9 years) with severe Crohn's diagnosed at the age of 26 months, currently UC or Crohn's colitis
*Current mediacation: IVIG, Humira, Azathpriorine, Eusaprim
(Tested but failed: Modulen IBD, Neocate advance, Budenofalk, Remicade, Azathpriorine, MTX, Jerusalem cocktail, cycklosporine, pentasa,...)
11-10-2014, 03:35 PM   #14
Pilgrim
Senior Member
 
Pilgrim's Avatar
 
Join Date: Jul 2014
Location: Ontario

My Support Groups:
Malgrave, how did they test for the mycobacterial infection?

I wonder if it's a standard test?
11-10-2014, 04:24 PM   #15
Malgrave
Senior Member
 
Malgrave's Avatar
 
Join Date: Jul 2012
Location: Belgium

My Support Groups:
I don't know if there are standard tests available at the moment. In my son's case they tried to culture intestinal TB, result negative. And they were able to identify Mycobacterium avium complex (I guess it was that) based on some sort of PCR test. I have also heard that if you have a MAP infection, your MAC test can be positive. Professor Hermon-Taylor is developing a MAP diagnostic test and I have high hopes for that.
11-11-2014, 06:16 AM   #16
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
I will have to pull the scope pics.
His scope looked visually normāl at dx.
So much so they were taking functional disease ( IBS)
The granulomas were found on the random biopsies in his TI and caecum.
11-11-2014, 08:52 AM   #17
Pilgrim
Senior Member
 
Pilgrim's Avatar
 
Join Date: Jul 2014
Location: Ontario

My Support Groups:
So, I'm wondering if the lyphangitis nodosa associated with the granulomas - being potentially irreversible - mean that granulomas also don't reverse.

Which is why I was wondering if there had been changes seen in anyone post treatment, on a biopsy level.

In our situation, I haven't ok'd another scope. Last one was earlier this year.
11-11-2014, 12:43 PM   #18
my little penguin
Forum Monitor
 
Join Date: Apr 2012

My Support Groups:
Prior to biologics inflammation could be seen on scopes 2 & 3
After biologics
Scope #4 was clean plus no granulomas found but things looked good mostly normal
- no way to know if they picked the right areas but other area ( sigmoid /rectum had improved ) duodendum was the only area still inflamed on biopsies.

He has been in remicAde and now humira
Reply

Crohn's Disease Forum » Books, Multimedia, Research & News » Granulomas obstruct lymphatics in all layers of the intestine in Crohn's disease.
Thread Tools


All times are GMT -5. The time now is 11:16 PM.
Copyright 2006-2017 Crohnsforum.com